ALG3 Mannosyltransferase

Abstract

N-Linked glycosylation is an essential eukaryotic protein modification. An oligosaccharide consisting of 14 sugar residues is synthesized at the endoplasmic reticulum (ER) membrane before being transferred to a protein (Kornfeld and Kornfeld 1985; Varki 1996; Burda and Aebi 1999). Dolichol phosphate is used as a lipid carrier for the synthesis, which is initiated by the addition of phospho-GlcNAc forming GlcNAc- pyrophosphate-dolichol (GlcNAc-PP-Dol). This is followed, in order, by additions of another GlcNAc, nine mannose, and three glucose residues. On the cytoplasmic side of the ER, activated sugars (UDP-GlcNAc and GDP-Man) are the donors for the two GlcNAc and first five mannose additions, respectively. The Man₅GlcNAc₂-PP-Dol is then translocated across the membrane into the ER lumen, where dolichol-phosphate- mannose-dependent mannosyltransferases sequentially add four mannose residues. (For further information on Dol-P-Man, see Chapter 78). The synthesis is completed by the transfer of three glucose residues from Dol-P-Glc to the oligosaccharide. (For a description of Dol-P-Glc-dependent transferases, see Chapter 82). The Glc₃Man₉GlcNAc₂ oligosaccharide is transferred to nascent glycoproteins by the oligosaccharyltransferase complex (see Chapter 83).